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MARCKS is an actin filament crosslinking protein regulated by protein kinase C and calcium–calmodulin

Nature volume 356, pages 618–622 (1992)Cite this article

Abstract

AGONISTS that stimulate protein kinase C (PKC) induce profound changes in cell morphology correlating with the reorganization of submembranous actin1,2, but no direct connection between PKC and actin assembly has been identified3. The myristoylated, alanine-rich C kinase substrate (MARCKS) binds calmodulin4,5 and is a predominant, specific substrate of PKC which is phosphorylated during macrophage and neutrophil activation6–8, growth factor-dependent mitogenesis9,10and neurosecretion11,12; it is redistributed from plasma membrane to cytoplasm when phosphorylated13–15 and is involved in leukocyte motility14,15. Here we report that MARCKS is a filamentous (F) actin crosslinking protein, with activity that is inhibited by PKC-mediated phosphorylation and by binding to calcium–calmodulin. MARCKS may be a regulated crossbridge between actin and the plasma membrane, and modulation of the actin crosslinking activity of the MARCKS protein by calmodulin and phosphorylation represents a potential convergence of the calcium–calmodulin and PKC signal transduction pathways in the regulation of the actin cytoskeleton.

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Author notes

  1. M. Thelen

    Present address: The Theodor Kocher Institute, University of Bern, CH-300, Bern, 9, Switzerland

Authors and Affiliations

  1. Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, 02115, USA

    J. H. Hartwig & P. A. Janmey

  2. Department of Anatomy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, 02115, USA

    J. H. Hartwig

  3. Department of Biological Chemistry and Molecular Pharmacology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, 02115, USA

    P. A. Janmey

  4. The Rockefeller University, 1230 York Avenue, New York, New York, 10021, USA

    M. Thelen, A. Resen, A. C. Nairn & A. Aderem

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  1. J. H. Hartwig
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  5. A. C. Nairn
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  6. A. Aderem
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Hartwig, J., Thelen, M., Resen, A. et al. MARCKS is an actin filament crosslinking protein regulated by protein kinase C and calcium–calmodulin. Nature 356, 618–622 (1992). https://doi.org/10.1038/356618a0

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